1. Curation of models: Painstaking effort or rewarding activity? Harish Dharuri Tuesday, October 27, 2015 Second Biomodels.net Training Camp

2. What makes it painstaking… Incomplete information in the paper  Missing Initial Conditions Parameter values Lack of correspondence between simulation result and figures given in the paper. Typo’s in model equations or just outright wrong representation. Unresponsive authors.

3. What makes it painstaking… Software issues: SBML compliance. Balance the need to make models compatible across the spectrum with aesthetics of model representation.

4. What makes it rewarding… and there are many reasons Learning

5. Examples in Model Integration Yeast Pheromone Pathway and Cell Cycle  BIOMD0000000032 and BIOMD0000000056 Calcium Dynamics

6. Yeast Pheromone Pathway CDC28+Far1PP: Leads to Cell Cycle Arrest

7. Far1PP-CDC28 time profile

8. Budding Yeast Cell Cycle, Chen et al (2004)

9. Time Series – Cell Cycle Model

10. Kegg Pathway

11. CLN1,2,3 Mutant – G1 Arrest

12. Recap What we are doing…  Merging the Yeast Pheromone model and the Cell cycle model.  Far1PP-CDC28 (ComplexN) inhibits Cyclins (CLN1, CLN2 and CLN3) in the cell cycle model. Inference made from literature. What we hope to see…  Cell cycle stop in the G1 phase. Needs to look like experimental data from CLN (1,2,3) mutants.

13. Dynamics of the Merged Model - DNA synthesis Introduction of Pheromone mating factor

14. Dynamics of the Merged Model – CKI profile Introduction of Pheromone mating factor

15. Calcium signaling pathway

16. Conclusions What makes it painstaking  Issues with Publications Software Authors don’t like me  What makes it rewarding  Offers a terrific learning experience  Ideal training for a Systems Biology aspirant

17. Conclusions Another Issue  Employability with this skill set What is the market demand/perception